Extrathymic induction of Foxp3⺠regulatory T cells declines with age in a T-cell intrinsic manner.
Eur J Immunol
; 43(10): 2598-604, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23824593
ABSTRACT
Extrathymically induced Foxp3⺠regulatory T (Treg) cells contribute to the pool of Treg cells and are implicated in the maintenance of immune tolerance at environmental interfaces. The impact of T-cell senescence on their generation and function is, however, poorly characterized. We report here that steady-state induction of Foxp3 is impaired in aged T cells in vivo. In vitro assays further revealed that this defective generation of Treg cells was independent from the strength of TCR stimulation and arose before T-cell proliferation. Importantly, they also revealed that this impairment of Foxp3 induction is unrelated to known age-related T-cell defects, such as IL-2 secretion impairment, accumulation of activated T-cell populations, or narrowing of the T-cell repertoire. Finally, a loss of extrathymic induction of Foxp3 and tolerance to minor-mismatched skin graft were observed in aged mice treated by nondepleting anti-CD4 antibody. The T-cell intrinsic impairment of Treg-cell generation revealed here highlights age as a key factor to be considered in immune tolerance induction.
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Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
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Subpopulações de Linfócitos T
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Transplante de Pele
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Senescência Celular
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Linfócitos T Reguladores
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article